A vaccine composed of cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM) covalently linked to tetanus toxoid was well tolerated and immunogenic in 25 normal volunteers given 25 mcg of polysaccharide and 25 given 50 mcg. There was no significant difference in the response between the two doses. Repeating the 25 or 50 mcg dose at 6 weeks did not significantly increase either the IgG or IgM antibody concentration. In mice, this vaccine conferred 70-80% protection against infection in mice pretreated either with the vaccine or serum from mice immunized with the vaccine.